Original Investigation
Utility of Nontraditional Risk Markers in Atherosclerotic Cardiovascular Disease Risk Assessment

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Abstract

Background

The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.

Objectives

This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle–brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis).

Methods

The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell’s C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease–related death, or fatal or nonfatal stroke.

Results

Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell’s C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell’s C statistic when added to the cPCE.

Conclusions

CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.

Key Words

ankle–brachial index
coronary artery calcium
high-sensitivity C-reactive protein
pooled cohort equation

Abbreviations and Acronyms

ABI
ankle–brachial index
ACC
American College of Cardiology
AHA
American Heart Association
ASCVD
atherosclerotic cardiovascular disease
CAC
coronary artery calcium
CHD
coronary heart disease
CI
confidence interval
cPCE
calibrated pooled cohort equation
CT
computed tomography
DM
diabetes mellitus
FH
family history
hsCRP
high-sensitivity C-reactive protein
MI
myocardial infarction
NRI
net reclassification improvement
PCE
pooled cohort equation

Cited by (0)

This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040 and UL1-RR-025005 from the National Center for Research Resources. Dr. Psaty served on the Drug Safety Monitoring Board for a clinical trial funded by the device manufacturer (Zoll LifeCor) and served on the Drug Safety Monitoring Board of the Yale Open Data Access Project funded by Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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